Adhantoro Rahadyan

Esnawan Antariksa Hospital

 The indications for implantable cardioverter-
defibrillators (ICDs) for the prevention of sudden
cardiac death have rapidly expanded over the past
10 years based on several RCT

 The optimal timing of defibrillator insertion after

myocardial infarction remains unresolved
Biochemical and electrophysiological factors
 Acute myocardial ischaemia is accompanied by significant intracellular and
extracellular ionic and metabolic alterations of the myocardial syncytium.
Extracellular changes include: elevated potassium, lysophosphoglycerides and
adenosine concentrations, increased lactate and carbon dioxide production,
acidosis, and catecholamine release. Concomitantly, intracellular changes include:
acidosis, elevated cyclic adenosine monophosphate (cAMP), and elevated
concentrations of calcium, magnesium, and sodium ion.*
Autonomic nervous system
 The pathophysiological role of the autonomic nervous system (ANS) in
arrhythmogenesis has been firmly established both experimentally and
clinically.**
 Within minutes of myocardial ischaemia there is a striking surge of sympathetic
nerve activity caused by a combination of pain, anxiety and reflex activation,
which has been demonstrated to be inversely related to left ventricular ejection
fraction
*Corr PB, Yamada KA. Selected metabolic alterations in the ischemic heart and their
contributions to arrhythmogenesis. In: Zehender M, Meinertz T, Just H. (eds)
Myocardial Ischaemia and Arrhythmia. New York: Steinkopff Darmstadt, 1994; 15–
33
** Schwartz PJ. The autonomic nervous system and sudden death. Eur Heart
J1998; 19 (Suppl F): F72–803.
 In the post-infarction period, impaired vagal tone, as
documented by decreased baroreflex sensitivity and heart
rate variability, has been associated with increased
inducibility of sustained monomorphic ventricular tachycardia
and with sudden death.***

***(La Rovere MT, Bigger Jr JT, Marcus FI, Mortara A, Schwartz PJ. Baroreflex sensitivity
and heart-rate variability in prediction of total cardiac mortality after myocardial infarction.
ATRAMI (Autonomic Tone and Reflexes After Myocardial Infarction)
Investigators. Lancet 1998; 351: 478–84)
 5% to 10% of hospitalized patients may develop
ventricular tachycardia (VT)/ventricular fibrillation (VF),
usually within 48 hours

 A study of 277 consecutive patients with NSTE-ACS

who underwent cardiac catheterization within 48
hours found VT/VF occurring in 7.6% of patients, 60%
of which developed within 48 hours after admission

2014 AHA/ACC NSTE- ACS Guideline

In the Valsartan in Acute Myocardial
Infarction
Trial (VALIANT), the risk of sudden
death was highest in the first 30
days after an MI ; 1.4% per month
Acute management of MI found a 90-day
cardiovascular mortality rate of 9%
 75% of the deaths judged to be coronary artery
disease-related nonsudden death,
 9% coronary artery disease-related sudden death,
and
 4% due to sudden death not related to coronary
artery disease
In multivariate analysis
 90 days, mortality was higher for patients with
ventricular tachyarrhythmias compared with those
patients without ventricular tachyarrhythmias
(23.6% vs 3.6%, adjusted HR: 3.63; 95% CI: 2.59–
5.09
 Medical
 Revascularization
 Radiofrequency catheter ablation
 Cardiac Device ( ICD)

Primary Secondary
Prevention Prevention
 Trial Year Patient LVEF Additional Study Hazard 95% CI p
s Features Ratio*
(n)
MADIT I 1996 196 < 35% NSVT and EP+ 0.46 (0.26-0.82) p=0.009
MADIT II 2002 1232 < 30% Prior MI 0.69 (0.51-0.93) p=0.016
CABG- 1997 900 < 36% +SAECG and CABG 1.07 (0.81-1.42) p=0.63
Patch
DEFINITE 2004 485 < 35% NICM, PVCs or 0.65 (0.40-1.06) p=0.08
NSVT
DINAMIT 2004 674 < 35% 6-40 days post-MI 1.08 (0.76-1.55) p=0.66
and Impaired HRV
SCD-HeFT 2006 1676 < 35% Prior MI of NICM 0.77 (0.62-0.96) p=0.007
AVID 1997 1016 Prior cardiac NA 0.62 (0.43-0.82) NS
arrest
CASH† 2000 191 Prior cardiac NA 0.766 ‡ 1-sided
arrest p=0.081
CIDS 2000 659 Prior cardiac NA 0.82 (0.60-1.1) NS
arrest,
syncope
* Hazard ratios for death from any cause in the ICD group compared with the non-ICD group. Includes only ICD and amiodarone patients from CASH.
‡CI Upper Bound 1.112 CI indicates Confidence Interval, NS = Not statistically significant, NSVT = nonsustained ventricular tachycardia, SAECG =
signal-averaged electrocardiogram.
Epstein A, et al. ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities. J Am Coll Cardiol 2008; 51:e1–62. Table
Patients with prior MI within 30 days and LVEF < 30% randomized in a 3:2
ratio
71 US centers and 5 European centers

Implantable defibrillator Conventional medical therapy

(n=742) (n=490)

All Cause Mortality - Average follow-up of 20 months

Stopped early by Data Safety Monitoring Board

 Study terminated November 20, 2001
 1232 patients randomised
◦ 742 defibrillator, 490 conventional
 Mean follow-up 20 months (range 6 days
- 53 months
 105 deaths in ICD group (14.2%)
 97 deaths in conventional group (19.8%)
 31% reduction in risk of death with ICD
Moss et al New Engl J Med 2002; 346: 877-883
 ACE inhibitors used in 70%
  blockers used in 70%
 Statins used in 68%
 57% had previously had CABG
 44% had previously had PTCA
◦ MADIT-2 targeted patients who were considered
suitable for CABG / PTCA
◦ Benefit of ICD is over & above benefit from
revascularisation
 Death
Avg. follow-up=20 months
P=0.016
25%

19.8% Hazard
20%
Ratio =
0.65
15% 14.2%

10%

5%

0%
Conventional ICD
Therapy
 Non Cardiac Cardiac Arrhythmic Non Arrhythmic

15% 13.7%

10.0%
10% 9.4%

5.5%
5% 4.1% 3.6% 3.7%
3.5%

0%
Conv ICD Conv ICD Conv ICD Conv ICD
Therapy Therapy Therapy Therapy
2521 patients with NYHA Class II or III HF, ICM, or NICM and
LVEF ≤ 35% •
Randomized to
1) conventional rx for HF + placebo;
2) conventional rx + amiodarone; or
3) conventional rx + conservatively programmed shockonly
single lead ICD •

• No survival benefit for amiodarone •

• 23% ↓ in overall mortality with ICD therapy •
• Absolute ↓ in mortality of 7.2% after 5 y in the overall
population

Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverter-defibrillator for
congestive heart failure. N Engl J Med
 Primary prevention with the ICD :
Patients with the larger QRSd benefit the
most

MADIT II

N Engl J Med, March 21, 2002

 In a MADIT-II substudy of 951 patients with prior
coronary revascularization, an ICD was of benefit
only in patients enrolled at least 6 months after
revascularization

HRS/ACC/AHA Expert Consensus Statement onthe Use of

Implantable Cardioverter-DefibrillatorTherapy
 674 patients 6 to 40 days post-MI with LVEF ≤ 35%
and impaired cardiac autonomic function
 Randomized to ICD therapy (n=332) or no ICD
therapy (n=342)
 Arrhythmic death ↓ in ICD group, but ↑ in
nonarrhythmic death (6.1% per year vs. 3.5% per
year, HR 1.75 (95% CI 1.11 to 2.76; p=0.016)
 No difference in total mortality
 In DINAMIT, only 50% of the sudden deaths were
attributable to arrhythmia, whereas mechanical
causes of SCD (eg, LV rupture, acute mitral
regurgitation) were observed in the other half of
patients.

HRS/ACC/AHA Expert Consensus Statement onthe Use of

Implantable Cardioverter-DefibrillatorTherapy
 Data from the VALIANT trial
showed the SCD risk is highest
in the first 30 days post MI

 With each 5% decrease in LVEF,

there was 21% increase in
relative risk of SCD during this
period

 SCD risk decrease with time

and plateau at 12 months
equalized between different
LVEF categories.

 This temporal trend is also

noted in combined analysis of
other trials (EMIAT, CAMIAT,
SWORD, TRACE, DIAMOND-MI)
 The benefit of ICD early vs late post MI does not seem to
be similar.

 Potent reduction in total mortality by ICD has been

confirmed when implemented in a ICM population with
remote MI.

 Although SCD risk is highest early post MI, ICD does not
impact total mortality. ICD merely changes the mode of
death from arrhythmic death to non-arrhythmic/heart
failure death.

 It seems that remodelling of ventricle early post MI

negates the ICD benefits, yet in late post MI when the
substrate becomes stable with healed scar tissue, re-
entrant arrhythmia is the primary mechanism for mortality
when ICD can significantly impact survival.
 ICD therapy is indicated before discharge in
patients who develop sustained VT/VF more than
48 hours after STEMI, provided the arrhythmia is
not due to transient or reversible ischemia,
reinfarction, or metabolic abnormalities*

*2013 ACC/AHA Guideline for the Management of ST-Elevation Myocardial Infarction

 I IIa IIb
IIbIII
III ICD therapy is indicated in patients who are survivors of
cardiac arrest due to ventricular fibrillation or
hemodynamically unstable sustained VT after evaluation
to define the cause of the event and to exclude any
completely reversible causes.
ICD therapy is indicated in patients with LVEF less than
35% due to prior MI who are at least 40 days post-MI and
are in NYHA functional Class II or III.
ICD therapy is indicated in patients with LV dysfunction due
to prior MI who are at least 40 days post-MI, have an LVEF
less than 30%, and are in NYHA functional Class I.

All primary SCD prevention ICD recommendations apply only to patients who are receiving optimal medical
therapy and have reasonable expectation of survival with good functional capacity for more than 1 year.

2008 ACC/AHA Guideline

 ‘Primary Prevention’:
◦ Previous MI and all of the following:
 Non-sustained VT on 24 hour ECG monitoring
 Inducible VT on electrophysiological testing
 LV ejection fraction < 35%, NYHA Class > 3
◦ A familial condition with a high risk of sudden death, e.g.
Long QT, HOCM, Brugada syndrome, ARVD, repaired
tetralogy of Fallot
www.nice.org.uk September 2000
 Implantasi DKI diharuskan pada:

 1. Pasien dengan FEVKi ≤35% dan kelas fungsional II atau III

NYHA, yang disebabkan IM, paling cepat 40 hari setelah
kejadian serangan jantung.

 2. Pasien dengan FEVKi ≤30% dan kelas fungsional I NYHA,

yang disebabkan IM, paling cepat 40 hari setelah kejadian
serangan jantung.

 3. Pasien yang selamat dari kejadian henti jantung karena FV

atau TV yang menetap dengan hemodinamik tidak stabil,
dan tidak ditemukan penyebabnya yang reversibe

PEDOMAN TERAPI MEMAKAI ALAT ELEKTRONIK KARDIOVASKULAR IMPLAN (ALEKA), PERKI 2014
 In patients within 90 days of revascularization who
have previously qualified for the implantation of an
ICD for secondary prevention of sudden cardiac
death (resuscitated from cardiac arrest due to
ventricular tachyarrhythmia) and have abnormal
left ventricular function, implantation of an ICD is
recommended.

HRS/ACC/AHA Expert Consensus Statement on

the Use of Implantable Cardioverter-Defibrillator
Therapy
 In patients who are within 90 days of
revascularization and who previously qualified for
the implantation of an ICD for primary prevention
of sudden cardiac death, and who have
undergone revascularization that is unlikely to
result in an improvement in LVEF >0.35, and who
are not within 40 days after an acute MI,
implantation of an ICD can be useful

HRS/ACC/AHA Expert Consensus Statement onthe Use

of Implantable Cardioverter-DefibrillatorTherapy
2015 ESC Guidelines for the management of the management of patients with ventricular
Arrhytmias and the prevention of suddent cardiac death
 Aggressive therapy to reduce the risk of sudden
cardiac death in the early period after MI directed
toward revascularization and improvement in
left ventricular function and clinical heart failure
can be a more prudent and effective strategy as
compared with early ICD implantation

HRS/ACC/AHA Expert Consensus Statement onthe Use of Implantable

Cardioverter-DefibrillatorTherapy
 Radiofrequency catheter ablation at a specialized
ablation centre followed by the implantation of an
ICD should be considered in patients with recurrent
VT, VF or electrical storms despite complete
revascularization and optimal medical treatment.

2015 ESC Guidelines for the management of patients with ventricular

arrhythmias and the prevention of sudden cardiac death
 Ambulatory ECG is indicated when there is a need to
clarify the diagnosis by detecting arrhythmias, QT-interval
changes, T-wave alternans (TWA), or ST changes to
evaluate risk, or to judge therapy. (Class I level A)

 Event monitors are indicated when symptoms sporadic to

establish whether or not they are caused by transient
arrhythmias. (Class I level B)

 Implantable recorders are useful in patients sporadic

symptoms suspected to be related to arrhythmias such as
syncope when a symptom-rhythm correlation cannot be
established by conventional diagnostic techniques. (Class
I level B)
Echocardiography is recommended in patients
 with ventricular arrhythmias who are suspected
of having structural heart disease. (Class I level B)

 at high risk for the development of serious

ventricular arrhythmias or SCD, such as those
with dilated, hypertrophic, or RV
cardiomyopathies, AMI survivors, or relatives of
patients with inherited disorders associated with
SCD. (Class I level B)
 EP testing is recommended in patients with
syncope of unknown cause with impaired LV
function or structural heart disease.(Class I level B)

 EP testing can be useful in patients with syncope

when bradyarrhythmias or tachyarrhythmias are
suspected and in whom noninvasive diagnostic
studies are not conclusive.(Class IIa level B)
 ICD therapy has clearly been shown to be effective
in aborting sudden arrhythmic death

 In patients with a prior Myocardial infarction and

advanced left ventricular dysfunction, prophylactic
implantation of defibrillator improves survival and
should be considered as a recommended therapy
 For early post MI patients, the management directive
is to maximize optimal medical therapy and
revascularization (early if not primary), and re-evaulate
LVEF at 40 days post MI or revascularization for
indication of ICD .

 For stable ischemic cardiomyopathy patient, LVEF still

provide the most validated and powerful risk
assessment to guide the need for prophylactic ICD.
 40 d

ICD 90 d

ICD

ICD
Second Prev
Primary Prev

ICD
 In the past, EP testing was considered the
primary method for risk stratification for
malignant ventricular arrhythmia.

 The value of EP testing is challenged in MUSTT-

EPS registry (n=1397) and MADIT II EP substudy
(n=593).

 Although EP testing does stratify CAD patients at

risk of SCD, its ability to do so is only modest.
◦ MUSTT-EPS: non-inducible = 12% arrhythmic death at 2
yr. (NPV 88% at 2 year)
◦ MADIT II EP: non-inducible = 25.5% ICD Rx at 2 yr. (vs
29.4% for inducible patients NS)
 Late potential represents low
amplitude high frequency electrical
activity at the terminal portion of
QRS. Thought to be due to slow
conduction and delayed myocardial
activation, a marker of ischemic
substrate.

 The prognostic value of SAECG had

been reported. In MUSTT trial,
patients with abnormal SAECG has
higher rate of arrhythmic and total
mortality (36% vs 13% 5 yr incidence)
but the sensitiviy and specificity
was inadequate to guide ICD
therapy